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PKCtheta Contributes to Myotube Formation by Regulating Protein Synthesis
Author(s) -
Marino Joseph S,
Hinds Terry,
Hoover Rachael A,
Ondrus Eric,
Onion Jeremy L,
Dowling Abigail,
McLoughlin Thomas,
Sanchez Edwin R,
Hill Jennifer W
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1152.20
Subject(s) - protein kinase c , myogenesis , phosphorylation , skeletal muscle , tyrosine phosphorylation , microbiology and biotechnology , insulin receptor , irs1 , mapk/erk pathway , myocyte , medicine , biology , endocrinology , chemistry , insulin , insulin resistance
The insulin signaling cascade regulates skeletal muscle protein synthesis. Protein kinase C theta (PKCθ) negatively regulates the insulin signaling cascade. Here we determine the role of PKCθ in myotube formation, a process critical to muscle development, regeneration, and hypertrophy. Using sh‐RNA, we established C 2 C 12 cells with 75% reduction in PKCθ (PKCθKD). PKCθKD myoblasts had enhanced fusion and myotube density, and increased protein synthesis following 4 days of differentiation. Phosphorylation of IRS1ser1101, a PKCθ inhibitory target, was reduced in PKCθKD 4 day old myotubes. Phosphorylation of IRS1ser636/639, substrates of ERK which promote IRS1 degradation, was increased in PKCθKD myotubes and supported by increased ERK activation. Surprisingly, insulin receptor (IR) tyrosine phosphorylation was reduced in PKCθKD myotubes, suggesting insulin resistance. However, PKCθKD and control myotubes both responded to insulin by increasing AKTser473 phosphorylation indicating insulin sensitivity. These findings suggest that reduced IR tyrosine and increased IRS1 serine phosphorylation in PKCθKD myotubes may be the result of protein synthesis negative feedback. Taken together, PKCθ contributes to the events of myotube formation by regulating protein synthesis. Future work is warranted to pursue PKCθ as a viable target to enhance skeletal muscle regeneration and hypertrophy in vivo.